血管加壓素轉化酶插入/缺失基因多型性與漢民族口腔癌相關性之探討

Angiotensin-converting enzyme gene insertion/deletion polymorphism in Chinese oral cancer patients

林岱蔚(Tai-Wei Lin)

指導教授 ： 謝天渝

高雄醫學大學/口腔醫學院/牙醫學研究所/碩士(2007年)

摘要

研究目的：
由於之前對血管加壓素轉化酶(ACE)插入/缺失(I/D)基因多型性對口腔癌前病變間有顯著關係，繼續探討ACE I/D基因多型性與口腔癌患者(實驗組)、和無口腔黏膜病變者（對照組）之關聯性。以及針對ACE 基因多型性嚼食檳榔且罹患口腔癌者間對疾病嚴重程度的關聯性，並進一步探討ACE I/D基因多型性與口腔癌及病嚴重程度之相關性。
研究方法：
以高雄醫學大學附設中和紀念醫院口腔顎面外科經病理診斷確定為口腔癌患者作為研究實驗組，沒有口腔黏膜疾病者作為對照，配對其年齡、性別各收案100人。收集其基本資料後採集靜脈全血進行DNA萃取，利用聚合酶連鎖反應(Polymerase chain reaction)進行ACE I/D基因多型性分析。
結果：
ACE I/D基因多型性在實驗組及對照組的分佈如下； II:ID:DD分別為34.2%:17.1%: 48.7%(實驗組),76.6%:15.6%:7.8%(對照組), p-value＜0.0001; D allele frequency分別為57.2%及15.7%, p-value＜0.0001，D allele在口腔癌組中有統計上的差異。在口腔癌患者中，AgII基因型可能在頭頸部林巴有轉移的傾向(adjusted p-value=0.05)。
結論：
血管加壓素轉化酶的基因多型性在口腔癌患者對健康對照組有顯著較高比率的DD基因型，由於血管加壓素對細胞分化和血管增生有促進作用，D allele對AngII的分泌比I allele者多50%，可以得知DD基因型將促進長期暴露於刺激的口腔黏膜細胞產生癌化的進程。另外DD基因型亦會與口腔癌頭頸部淋巴轉移相關(p-value=0.05)。以上結果顯示ACE I/D基因多型性在口腔癌之致病機轉中，可能扮演相當程度之角色。

關鍵字

血管加壓素轉化酶基因多型性 ； 感受性 ； 口腔癌 ； 檳榔

並列摘要

Objective：
Earlier, our research shows that angiotensin converting enzyme(ACE) insertion/deletion(I/D) gene polymorphism is significantly related to oral precanceous lesion. We continue to investigate the connection between ACE I/D gene polymorphism oral cancer patient(experiment group) compared with non-oral mucosal lesion patient(control group), and the relation of severity of oral cancer on betel nut chewing patients. We test the hypothesis that ACE I/D gene polymorphism participates in oral cancer prevalance and disease severity.

Materials & Methods：
Using genomic DNA from 111 patients with oral cancer(most are squamous cell carcinoma), we assessed the ACE I/D gene polymorphism by PCR analysis and compared with a noncancer control population(n = 115)
Results：
ACE genotypes are distributed in patients and control subjects as follows; DD is present in 54(48.7%), ID in 19(17.1%), and in 38(34.2%) patients, and DD in 9(7.8%), ID in 18(15.6%), and in 88(76.6%) healthy subjects repectively(p-value<0.005). In oral cancer patients, trend was observed between angiotensin II genotypes and lymph node metastasis in head and neck region(p-value = 0.05).
Conclusions：
ACE I/D gene polymorphism presents higher frequency in oral cancer patients than in cancer-free subjects. And the further analysis suggests the relation between Ag II and lymph node metastasis. Thus, ACE may influence the pathogenesis and disease progression in oral cancer.

並列關鍵字

Angiotensin-converting enzyme ； gene polymorphism ； susceptibility ； oral cancer ； betel nut

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